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Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons.

Gielen V, Sykes A, Zhu J, Chan B, Macintyre J, Regamey N, Kieninger E, Gupta A, Shoemark A, Bossley C, Davies J, Saglani S, Walker P, Nicholson SE, Dalpke AH, Kon OM, Bush A, Johnston SL, Edwards MR - J. Allergy Clin. Immunol. (2015)

Bottom Line: SOCS1 levels were also correlated with asthma-related clinical outcomes.Suppression of virus-induced interferon levels was dependent on SOCS1 nuclear translocation but independent of proteasomal degradation of transcription factors.Nuclear SOCS1 levels were also increased in BECs from asthmatic patients.

View Article: PubMed Central - PubMed

Affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom; Centre for Respiratory Infection, Imperial College London, London, United Kingdom.

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SOCS1 overexpression inhibited IFN-β–induced IFN-β and IFN-λ1 promoter activation and activation of minimal promoters containing ISRE and STAT1/2 binding sites. Human BECs were transfected with plasmids encoding SOCS1 or empty vector pORF. A and B, IFN-β (5 ng/mL) induced IFN-β promoter activation (Fig E3, A) and IFN-λ1 promoter activation (Fig E3, B) at 24 hours, which were both significantly suppressed by SOCS1 (n = 4 experiments). BEAS-2B cells were transfected with plasmids encoding SOCS1 or empty vector pORF. SOCS1 also inhibited both IFN-β (5 ng/mL)–induced IFN-β promoter activation (Fig E3, C) and IFN-λ1 promoter activation (Fig E3, D) at 24 hours. E and F, SOCS1 also inhibited IFN-β–induced ISRE-driven promoter activation (Fig E3, E) and STAT1/2-driven promoter activation (Fig E3, F) at 24 hours. Values are presented as means ± SEMs (n = 3 experiments). *P < .05, **P < .01, and ***P < .001, as indicated, by using 1-way ANOVA with the Bonferroni multiple comparison test.
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dfig3: SOCS1 overexpression inhibited IFN-β–induced IFN-β and IFN-λ1 promoter activation and activation of minimal promoters containing ISRE and STAT1/2 binding sites. Human BECs were transfected with plasmids encoding SOCS1 or empty vector pORF. A and B, IFN-β (5 ng/mL) induced IFN-β promoter activation (Fig E3, A) and IFN-λ1 promoter activation (Fig E3, B) at 24 hours, which were both significantly suppressed by SOCS1 (n = 4 experiments). BEAS-2B cells were transfected with plasmids encoding SOCS1 or empty vector pORF. SOCS1 also inhibited both IFN-β (5 ng/mL)–induced IFN-β promoter activation (Fig E3, C) and IFN-λ1 promoter activation (Fig E3, D) at 24 hours. E and F, SOCS1 also inhibited IFN-β–induced ISRE-driven promoter activation (Fig E3, E) and STAT1/2-driven promoter activation (Fig E3, F) at 24 hours. Values are presented as means ± SEMs (n = 3 experiments). *P < .05, **P < .01, and ***P < .001, as indicated, by using 1-way ANOVA with the Bonferroni multiple comparison test.

Mentions: We found that overexpression of SOCS1 in both primary human BECs and in the human BEC cell line BEAS-2B (see Fig E3 in this article's Online Repository at www.jacionline.org) completely inhibited exogenous IFN-β–induced activation of both the IFN-β and IFN-λ1 promoters. In BEAS-2B cells SOCS1 also suppressed interferon induction of a minimal promoter containing the interferon-stimulated response element (ISRE) and a minimal promoter containing a STAT1/2-responsive element (see Fig E3), which are type I interferon–responsive promoters induced by the interferon-stimulated gene factor 3 and STAT1/2 transcription factor complexes, respectively, and are typical readouts for interferon signaling.


Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons.

Gielen V, Sykes A, Zhu J, Chan B, Macintyre J, Regamey N, Kieninger E, Gupta A, Shoemark A, Bossley C, Davies J, Saglani S, Walker P, Nicholson SE, Dalpke AH, Kon OM, Bush A, Johnston SL, Edwards MR - J. Allergy Clin. Immunol. (2015)

SOCS1 overexpression inhibited IFN-β–induced IFN-β and IFN-λ1 promoter activation and activation of minimal promoters containing ISRE and STAT1/2 binding sites. Human BECs were transfected with plasmids encoding SOCS1 or empty vector pORF. A and B, IFN-β (5 ng/mL) induced IFN-β promoter activation (Fig E3, A) and IFN-λ1 promoter activation (Fig E3, B) at 24 hours, which were both significantly suppressed by SOCS1 (n = 4 experiments). BEAS-2B cells were transfected with plasmids encoding SOCS1 or empty vector pORF. SOCS1 also inhibited both IFN-β (5 ng/mL)–induced IFN-β promoter activation (Fig E3, C) and IFN-λ1 promoter activation (Fig E3, D) at 24 hours. E and F, SOCS1 also inhibited IFN-β–induced ISRE-driven promoter activation (Fig E3, E) and STAT1/2-driven promoter activation (Fig E3, F) at 24 hours. Values are presented as means ± SEMs (n = 3 experiments). *P < .05, **P < .01, and ***P < .001, as indicated, by using 1-way ANOVA with the Bonferroni multiple comparison test.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4541718&req=5

dfig3: SOCS1 overexpression inhibited IFN-β–induced IFN-β and IFN-λ1 promoter activation and activation of minimal promoters containing ISRE and STAT1/2 binding sites. Human BECs were transfected with plasmids encoding SOCS1 or empty vector pORF. A and B, IFN-β (5 ng/mL) induced IFN-β promoter activation (Fig E3, A) and IFN-λ1 promoter activation (Fig E3, B) at 24 hours, which were both significantly suppressed by SOCS1 (n = 4 experiments). BEAS-2B cells were transfected with plasmids encoding SOCS1 or empty vector pORF. SOCS1 also inhibited both IFN-β (5 ng/mL)–induced IFN-β promoter activation (Fig E3, C) and IFN-λ1 promoter activation (Fig E3, D) at 24 hours. E and F, SOCS1 also inhibited IFN-β–induced ISRE-driven promoter activation (Fig E3, E) and STAT1/2-driven promoter activation (Fig E3, F) at 24 hours. Values are presented as means ± SEMs (n = 3 experiments). *P < .05, **P < .01, and ***P < .001, as indicated, by using 1-way ANOVA with the Bonferroni multiple comparison test.
Mentions: We found that overexpression of SOCS1 in both primary human BECs and in the human BEC cell line BEAS-2B (see Fig E3 in this article's Online Repository at www.jacionline.org) completely inhibited exogenous IFN-β–induced activation of both the IFN-β and IFN-λ1 promoters. In BEAS-2B cells SOCS1 also suppressed interferon induction of a minimal promoter containing the interferon-stimulated response element (ISRE) and a minimal promoter containing a STAT1/2-responsive element (see Fig E3), which are type I interferon–responsive promoters induced by the interferon-stimulated gene factor 3 and STAT1/2 transcription factor complexes, respectively, and are typical readouts for interferon signaling.

Bottom Line: SOCS1 levels were also correlated with asthma-related clinical outcomes.Suppression of virus-induced interferon levels was dependent on SOCS1 nuclear translocation but independent of proteasomal degradation of transcription factors.Nuclear SOCS1 levels were also increased in BECs from asthmatic patients.

View Article: PubMed Central - PubMed

Affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom; Centre for Respiratory Infection, Imperial College London, London, United Kingdom.

Show MeSH
Related in: MedlinePlus